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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brussels sprouts (Brassica oleracea, L; Jade cross E, hybrid cultivar) were cultivated with inorganic selenium added to the plant growth medium. Sprague-Dawley, female, weanling rats were divided into groups and fed 20% brussels sprouts diets containing either 0.03, 0.58, 1.29, or 6.71 ppm of selenium naturally occurring in the sprouts. These diets were fed 2 weeks before and 2 weeks after a single dose of 7,12-dimethylbenz[a]anthracene (DMBA), and the rats were then placed on a low selenium basal diet for an additional 25 weeks. All brussels sprouts diets reduced the incidence of DMBA-induced mammary carcinogenesis. Increased dietary levels of naturally occurring selenium did not further depress mammary tumorigenesis. The time periods of selenium feeding may have been too brief to observe any additional tumor reductions.
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PMID:Effect of dietary brussels sprouts with increased selenium content on mammary carcinogenesis in the rat. 249 15

The effects of selenium intake on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis were examined in rats fed a diet high in mixed fats and representative of that consumed in North America. Six groups of 20 rats were fed an AIN-76 diet modified to contain 20% fat from lard:corn oil (3:1 wt/wt) and various amounts of selenium (0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet). At wk 5, animals in groups 2-6 were dosed with 4.32 mg of DMBA. Serum clinical parameters and the activities of plasma selenium-dependent and total glutathione peroxidase (GSHPx), erythrocyte GSHPx and superoxide dismutase (SOD) were determined every 4 wk for 25 wk. The extent of lipid peroxidation was determined by measuring urinary malondialdehyde during wk 13 and 24, and erythrocyte malondialdehyde at wk 25. Erythrocyte GSHPx was found to be a better indicator of selenium status than plasma activity, while SOD did not vary with dietary selenium. The group of animals fed 4.0 mg Se/kg diet had reduced numbers of tumors (P less than 0.01), but this reduction was associated with evidence of chronic selenium toxicity. Variations in GSHPx activity with dietary selenium did not result in differences in tumor incidence, nor in changes in lipid peroxidation in the other groups. Thus, nontoxic levels of selenium do not appear to offer any protective effect during carcinogenesis in rats fed a casein-based diet similar in fat content to that consumed by North Americans.
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PMID:Effects of dietary selenium on DMBA-induced carcinogenesis in rats fed a diet high in mixed fats. 249 71

Female weanling Sprague-Dawley rats were used to examine the changes that occurred in selenium and antioxidant status during the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Animals were fed an AIN-76 diet, modified to contain 20% fat (3:1 wt/wt, lard:corn oil) and 0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet. At wk 5, rats in groups 2-6 were administered by intragastric tube 4.32 mg of DMBA dissolved in corn oil. Control rats received corn oil only. A blood sample was removed from the tail vein and analyzed for selenium-dependent glutathione peroxidase (Se-GSHPx) and superoxide dismutase (SOD) activity at wk 5, and every 4 wk until wk 25. At the end of the experiment, rats were classified by tumor status, and each diet group was subdivided into two groups: those rats remaining free of tumors for 25 wk and those with tumors. DMBA treatment caused an initial decrease in erythrocyte SeGSHPx and SOD activity compared to untreated control rats. SeGSHPx activity in rats with tumors remained lower than controls, while SeGSHPX activity increased in rats with no tumors. These changes, however, were not associated with any changes in lipid peroxidation.
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PMID:Changes in selenium and antioxidant status during DMBA-induced mammary carcinogenesis in rats. 249 72

New approaches to enhancing D,L-alpha-difluoromethylornithine (DFMO) inhibition of DMBA-induced mammary tumorigenesis were investigated. It is reasoned that perturbation of a second regulatory element in polyamine biosynthesis, i.e., the generation of propylamine groups from S-adenosylmethionine (AdoMet), would potentiate the effectiveness of DFMO. Precursor availability for AdoMet was limited when rats were fed a low methionine diet. The diet of control rats was supplemented with 0.3% methionine. DFMO, when added to the diet at 0.1%, suppressed tumorigenesis, regardless of methionine levels, although its efficacy was significantly enhanced by the low methionine diet. Selenite, another effective chemopreventive agent in this tumor model, also requires AdoMet for its metabolism. However, the anticarcinogenic action of selenite is not compromised by low dietary methionine. The differential sensitivity of DFMO and selenium chemoprevention to low dietary methionine, therefore, provides an opportunity to test for an additive effect. Results of the combination regimen study showed that the incidence and yield of DMBA-induced mammary tumors were significantly lower in the two-agent protocol compared to either DFMO or selenite alone. The mechanism(s) that accounts for the heightened efficacy of combined DFMO and selenite chemoprevention will be discussed.
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PMID:New approaches to cancer chemoprevention with difluoromethylornithine and selenite. 249 24

A role for the dietary trace mineral element selenium in the reduction of cancer incidence has been documented in numerous epidemiological and experimental studies. The precise mechanism of this antitumor effect is not well understood, but published data suggest that both inhibition of tumor cell growth and enhancement of host immunity are likely to be involved. In this study we report that selenium at physiologic concentrations can inhibit human lymphocyte proliferation in response to irradiated tumor cells in mixed lymphocyte/tumor cell cultures (MLTC). In addition, we demonstrate that the various lymphocyte functional activities generated in these cultures exhibit different levels of sensitivity to the effects of selenium. The generation of suppressor-cell activity in MLTC was strongly inhibited by the presence of physiologic levels of selenium, while the development of cytotoxic T-lymphocyte activity in identical cultures was not affected by selenium. Production of interleukin-2 in these cultures showed an intermediate sensitivity to the effects of selenium. Thus, selenium appears to be capable of selectively regulating the generation of functional lymphocyte subsets in vitro. Such selective regulation could explain the published effects of selenium on immunity and would be consistent with a role for immunity in the observed reduction of cancer incidence associated with elevated selenium intake.
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PMID:Selenium and the immune response: 1. Modulation of alloreactive human lymphocyte functions in vitro. 252 90

Recent evidence supports the concept that Adriamycin cytotoxicity may be mediated by drug semiquinone free radical and oxyradical generation. We tested this hypothesis further by exposing drug-sensitive (WT) and 500-fold Adriamycin-resistant MCF-7 human breast tumor cells (ADRR) to exogenous superoxide- and hydrogen peroxide-generating systems and subsequently monitored cell proliferation as a measure of cytotoxicity. The ADRR tumor cells tolerated a 4-fold greater exposure than sensitive cells to superoxide generated by the xanthine/xanthine oxidase system. Likewise, exposure to hydrogen peroxide produced by the action of glucose oxidase on glucose revealed a 4-fold diminished susceptibility of the drug-resistant cells to this reduced form of oxygen. Similar results were obtained by the direct application of hydrogen peroxide to cells. For both cell lines, cytotoxicity was dependent upon the magnitude and the duration of reactive oxygen exposure. When WT and ADRR cells were cultured under hyperoxia (95% O2:5% CO2), in order to stimulate the intracellular production of oxyradicals, proliferation was inhibited to a greater extent in the drug-sensitive cell line. Additionally, hyperoxia potentiated the cytotoxicity of Adriamycin to both sensitive and drug-resistant cells, but the effect depended upon the concentration of the drug. Under hyperoxic conditions, Adriamycin caused oxygen radical-dependent cytotoxicity to the WT tumor cells at clinically relevant drug concentrations as low as 2 to 3 nM. With ADRR tumor cells, hyperoxia increased the cytotoxicity of Adriamycin at concentrations above 5 microM. Paradoxically, both the WT and the ADRR tumor cells were equally susceptible to the cytotoxic effects of gamma irradiation. It is known that the Adriamycin-resistant MCF-7 cells greatly overexpress glutathione peroxidase and glutathione transferase activities; however, other biochemical defenses against reactive drug intermediates and oxygen radicals have been reported to be similar in the two cell lines. We have reexamined those observations in this report. The resistance of ADRR breast tumor cells to Adriamycin appears to be associated with a developed tolerance to superoxide, most likely because of a twofold increase in superoxide dismutase activity, and a decreased susceptibility to hydrogen peroxide, most likely because of 12-fold augmented selenium-dependent glutathione peroxidase activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential oxygen radical susceptibility of adriamycin-sensitive and -resistant MCF-7 human breast tumor cells. 253 95

The effect of the dietary organoselenium compound, benzylselenocyanate (BSC) along with its sulphur analogue, benzylthiocynanate (BTC) and sodium selenite (Na2SeO3), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis was examined in female Sprague-Dawley rats during the initiation phase of carcinogenesis. Semipurified diets containing 25 p.p.m. of BSC and 25 p.p.m. BTC, and 4 p.p.m. Selenium as Na2SeO3 in drinking water were given to 5-week-old rats for 3 weeks starting 2 weeks before, during and until 1 week after carcinogen treatment. At 7 weeks of age animals were given a single dose of DMBA (10 mg) in 1 ml olive oil by oral intubation. One week after DMBA treatment, the groups receiving BSC- and BTC-supplemented diets were transferred to the unsupplemented standard diets and the group of rats receiving Na2SeO3 in drinking water was transferred to regular tap water for the duration of the experiment. The results indicate that the rats receiving BSC in their diet showed a highly significant inhibition of tumor incidence and tumor multiplicity as well as a prolonged latency period when compared to the group fed the control diet. Neither BTC nor Na2SeO3 had any effect on the subsequent development of mammary tumors. These results indicate that dietary BSC inhibits mammary tumor incidence during the initiation phase of carcinogenesis and is a considerably more potent inhibitor than its sulphur analogue BTC and inorganic selenium. This is the first report that demonstrates the inhibition of mammary carcinogenesis by a synthetic organoselenium compound.
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PMID:Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselenocyanate, in rats. 253 74

A new parameter, the ratio of lipid peroxide and vitamins E and C [LPO/(VE + VC)], has been proposed and used to reflect the balance between lipid peroxidation and antioxidation capability of cancer patients and of healthy human controls. The effects of vitamins E, C, and selenium on the serum LPO level in mice bearing Ascites Hepatomas (H22) have also been examined. The results showed that the average of LPO/(VE + VC) ratios in cancer patients (135 cases) was significantly higher than that of the normal controls (222 cases). The authors suggest that this ratio might be used as one of the parameters for early diagnosis and prognosis of diseases (including cancers) caused by free radicals and lipid peroxides. The results also showed that antioxidants - Se(Na2SeO3, 1mg/kg) or vitamin E (5mg/kg) could markedly decrease the level of serum LPO in the tumor-bearing animals. A smaller dose of VE (1mg/kg) and doses of Vc up to 300mg/kg showed no effect on the serum LPO levels when given separately. However, synergistic effects were observed when any 2 out of 3 or three nutrients were given together. Those with three nutrients significantly lowered the serum LPO level. These antioxidants also inhibited the proliferation of tumour cells.
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PMID:The relationship between nutritional antioxidants and serum lipid peroxides in cancer patients. 256 28

An inverse correlation between cancer incidence and dietary intake of the trace mineral element selenium has been well established in epidemiological and experimental studies. The mechanisms for this chemoprotective effect are unresolved. Much attention has been focused on the antiproliferative effects of selenium on various normal and neoplastic cell types. However, dietary selenium supplementation can also enhance the expression of various humoral and cellular immune responses. In examining the effects of dietary selenium on cell-mediated immunity in mice, we observed that selenium supplementation caused the enhanced expression of spontaneous natural killer (NK) cytotoxicity in spleen cells and of specific cytotoxic T-lymphocyte (CTL) cytotoxicity in peritoneal exudate cells (PEC). NK activity of spleen-cell suspensions from selenium-supplemented mice increased an average of 70% over that of the control group (basal diet). Cytotoxic activity of PEC from mice injected with tumors intraperitoneally peaked earlier in selenium-supplemented animals, and the appearance of cells staining positively for Thy 1.2 surface antigen in selenium-supplemented animals also preceded the values observed in control animals. We propose here that enhancement of in vivo cytotoxic mechanisms, is likely to act synergistically with tumor growth inhibition in the reduction of tumor incidence associated with selenium intake.
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PMID:Selenium and the immune response: 2. Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo. 256 12

In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-0-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU of retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP /g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion resulted in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased 0-fold, 1.4-fold, and 3.6-fold. Bone deformities were augmented 0-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium (2 ppm in the drinking water) did not alter the bone toxicity of RP. 13-cis-retinoic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidenced by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osteotoxicities were similar in the mice fed diets supplemented with RP and CRA. Thus, the light dose of CRA (700 IU/g diet) was less toxic than the high dose of, RP but at a lower dose (200 IU/g), CRA was as osteotoxic as was RP. Bone fractures in mice exposed to prolonged dietary administration of retinoids was a more sensitive index of retinoid toxicity than was body weight. We have detected osteotoxicity in mice at a total dose of CRA which was about twice the total dose used clinically.
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PMID:Osteotoxicity after chronic dietary administration of 13-cis-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion. 260 68


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